Precisely how the length of the female fertile lifespan is regulated is poorly understood and it is likely to involve complex factors, one of which is follicle number. Indeed, the duration of female fertility appears to be intimately linked to the number of available oocytes, which are stored in the ovary as primordial follicles. There is mounting evidence implicating the intrinsic apoptosis pathway, which is controlled by members of the B-cell lymphoma-2 (BCL-2) family, as a key regulator of the number of primordial follicles established in the ovary at birth and maintained throughout reproductive life. Consequently, the pro- and anti-apoptotic BCL-2 family proteins are emerging as key determinants of the length of the female fertile lifespan. This review discusses the relationship between the intrinsic apoptosis pathway, follicle number and length of the female fertile lifespan.